The ultimate goal of the work in this application is to develop a reliable, continuous subcutaneous glucose monitoring system. Sensor development technology over the past 20 years has resulted in production of potentially practical glucose electrodes. Given the risks associated with long-term intravascular placement of sensor electrodes, extravascular, subcutaneous placement appears to be the situation of choice. Reliability of extravascular devices, however, remains problematic because of the unstable relationship between blood glucose concentration and the extracellular glucose concentration at the sensor/tissue interface. In addition, substantial practical difficulties in vivo calibration must be surmounted. The continuous glucose monitoring system described in this application addresses the issue of reliability by: 1) applying measured tissue oxygen data to correct extracellular glucose measurements, thereby more adequately representing central blood glucose concentrations; and 2) continuously providing measurements of the uncertainties of the blood glucose calculations and in vivo response time based upon monitored conditions at the sensor/tissue interface. These features of the sensor system can be viewed as performing automatic "in vivo calibrations", while providing measurement uncertainty information which reflects the physiological status and integrity of the sensor/tissue interface. The applicant group has recently completed a phase II study of a self-calibrating in vivo blood gas, pH, and electrolyte monitor based upon a similar principle.